The emerging molecular pathogenesis of neuroblastoma: Implications for improved risk assessment and targeted therapy

Genome Medicine

Volumn 1, Issue 7, 2009, Pages

  Van Roy, Nadine ^a   De Preter, Katleen ^a   Hoebeeck, Jasmien ^a   Van Maerken, Tom ^a   Pattyn, Filip ^a   Mestdagh, Pieter ^a   Vermeulen, Joëlle ^a   Vandesompele, Jo ^a   Speleman, Frank ^a  

^a GHENT UNIVERSITY HOSPITAL   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; BRCA1 ASSOCIATED RING DOMAIN PROTEIN 1; CELL ADHESION MOLECULE 1; CHROMODOMAIN HELICASE DNA BINDING PROTEIN 5; CYCLIN DEPENDENT KINASE INHIBITOR 2A; DNA; GEFITINIB; IMATINIB; KINESIN FAMILY MEMBER 1B; MICRORNA; NON METASTATIC CELLS 1 PROTEIN; NUCLEOSIDE DIPHOSPHATE KINASE; ONCOPROTEIN; PAIRED LIKE HOMEOBOX 2B; PROTEIN PHOSPHATASE 1D MAGNESIUM DEPENDENT DELTA; PROTEIN TYROSINE KINASE; RAS ASSOCIATION DOMAIN FAMILY PROTEIN 1A; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG; V MYC MYELOCYTOMATOSIS VIRAL RELATED PROTEIN;

ALLELE; ANTINEOPLASTIC ACTIVITY; CANCER LOCALIZATION; CANCER MORTALITY; CHILDHOOD CANCER; CHROMOSOME 11Q; CHROMOSOME 1P; CHROMOSOME 3P; CHROMOSOME 7Q; CHROMOSOME LOSS; CHRONIC MYELOID LEUKEMIA; DNA CONTENT; DNA METHYLATION; DRUG TARGETING; ENZYME INHIBITION; FAMILIAL DISEASE; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE NUMBER; GENETIC ANALYSIS; GENETIC RISK; GENETIC SUSCEPTIBILITY; HUMAN; LUNG NON SMALL CELL CANCER; NEUROBLASTOMA; ONCOGENE MYC; PATHOGENESIS; PLOIDY; PRIORITY JOURNAL; PROGNOSIS; REVIEW; RISK ASSESSMENT;

EID: 77950840735     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/gm74     Document Type: Review

References (129)

1. Schwab M, Westermann F, Hero B, Berthold F: Neuro blas-toma: biology and molecular and chromosomal pathology. Lancet Oncol 2003, 4:472-480.
2. Brodeur GM: Neuroblastoma: biological insights into a clin-ical enigma. Nat Rev Cancer 2003, 3:203-216.
3. Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, Faldum A, Hero B, Iehara T, Machin D, Mosseri V, Simon T, Garaventa A, Castel V, Matthay KK: The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009, 27:289-297.
4. Monclair T, Brodeur GM, Ambros PF, Brisse HJ, Cecchetto G, Holmes K, Kaneko M, London WB, Matthay KK, Nuchtern JG, von Schweinitz D, Simon T, Cohn SL, Pearson AD: The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol 2009, 27: 298-303.
5. Ambros PF, Ambros IM, Brodeur GM, Haber M, Khan J, Nakagawara A, Schleiermacher G, Speleman F, Spitz R, London WB, Cohn SL, Pearson AD, Maris JM: International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer 2009, 100:1471-1482.
6. Bagatell R, Rumcheva P, London WB, Cohn SL, Look AT, Brodeur GM, Frantz C, Joshi V, Thorner P, Rao PV, Castleberry R, Bowman LC: Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy. J Clin Oncol 2005, 23:8819-8827.
7. George RE, London WB, Cohn SL, Maris JM, Kretschmar C, Diller L, Brodeur GM, Castleberry RP, Look AT: Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblas-toma: a Pediatric Oncology Group study. J Clin Oncol 2005, 23: 6466-6473.
8. Look AT, Hayes FA, Shuster JJ, Douglass EC, Castleberry RP, Bowman LC, Smith EI, Brodeur GM: Clinical relevance of tumor cell ploidy and N-myc gene amplification in child-hood neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol 1991, 9:581-591.
9. Kaneko Y, Knudson AG: Mechanism and relevance of ploidy in neuroblastoma. Genes Chromosomes Cancer 2000, 29:89-95.
10. Schwab M, Varmus HE, Bishop JM, Grzeschik KH, Naylor SL, Sakaguchi AY, Brodeur G, Trent J: Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc. Nature 1984, 308:288-291.
11. Wenzel A, Cziepluch C, Schurmann J, Schwab M: The N-myc oncoprotein is a transcriptional activator and associates with max and RB1 proteins. Prog Clin Biol Res 1994, 385:59-66.
12. Weiss WA, Aldape K, Mohapatra G, Feuerstein BG, Bishop JM: Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 1997, 16:2985-2995.
13. Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM: Amplification of N-myc in untreated human neuroblasto-mas correlates with advanced disease stage. Science 1984, 224: 1121-1124.
14. Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, Hammond D: Association of multiple copies of the N-myc oncogene with rapid progression of neuroblasto-mas. N Engl J Med 1985, 313:1111-1116.
15. Westermann F, Muth D, Benner A, Bauer T, Henrich KO, Oberthuer A, Brors B, Beissbarth T, Vandesompele J, Pattyn F, Hero B, Konig R, Fischer M, Schwab M: Distinct transcrip-tional MYCN/c-MYC activities are associated with sponta-neous regression or malignant progression in neuroblastomas. Genome Biol 2008, 9:R150.
16. White PS, Thompson PM, Gotoh T, Okawa ER, Igarashi J, Kok M, Winter C, Gregory SG, Hogarty MD, Maris JM, Brodeur GM: Definition and characterization of a region of 1p36.3 con-sistently deleted in neuroblastoma. Oncogene 2005, 24: 2684-2694.
17. Bauer A, Savelyeva L, Claas A, Praml C, Berthold F, Schwab M: Smallest region of overlapping deletion in 1p36 in human neuroblastoma: a 1 Mbp cosmid and PAC contig. Genes Chromosomes Cancer 2001, 31:228-239.
18. Caron H, Spieker N, Godfried M, Veenstra M, van Sluis P, de Kraker J, Voute P, Versteeg R: Chromosome bands 1p35-36 contain two distinct neuroblastoma tumor suppressor loci, one of which is imprinted. Genes Chromosomes Cancer 2001, 30:168-174.
19. Martinsson T, Sjoberg RM, Hallstensson K, Nordling M, Hedborg F, Kogner P: Delimitation of a critical tumour sup-pressor region at distal 1p in neuroblastoma tumours. Eur J Cancer 1997, 33:1997-2001.
20. Okawa ER, Gotoh T, Manne J, Igarashi J, Fujita T, Silverman KA, Xhao H, Mosse YP, White PS, Brodeur GM: Expression and sequence analysis of candidates for the 1p36.31 tumor suppressor gene deleted in neuroblastomas. Oncogene 2008, 27:803-810.
21. Schleiermacher G, Peter M, Michon J, Hugot JP, Vielh P, Zucker JM, Magdelenat H, Thomas G, Delattre O: Two distinct deleted regions on the short arm of chromosome 1 in neu-roblastoma. Genes Chromosomes Cancer 1994, 10:275-281.
22. Takeda O, Homma C, Maseki N, Sakurai M, Kanda N, Schwab M, Nakamura Y, Kaneko Y: There may be two tumor sup-pressor genes on chromosome arm 1p closely associated with biologically distinct subtypes of neuroblastoma. Genes Chromosomes Cancer 1994, 10:30-39.
23. Thompson PM, Gotoh T, Kok M, White PS, Brodeur GM: CHD5, a new member of the chromodomain gene family, is preferentially expressed in the nervous system. Oncogene 2003, 22:1002-1011.
24. Bagchi A, Papazoglu C, Wu Y, Capurso D, Brodt M, Francis D, Bredel M, Vogel H, Mills AA: CHD5 is a tumor suppressor at human 1p36. Cell 2007, 128:459-475.
25. Fujita T, Igarashi J, Okawa ER, Gotoh T, Manne J, Kolla V, Kim J, Zhao H, Pawel BR, London WB, Maris JM, White PS, Brodeur GM: CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst 2008, 100: 940-949.
26. Chen YZ, Soeda E, Yang HW, Takita J, Chai L, Horii A, Inazawa J, Ohki M, Hayashi Y: Homozygous deletion in a neuroblast-oma cell line defined by a high-density STS map spanning human chromosome band 1p36. Genes Chromosomes Cancer 2001, 31:326-332.
27. Munirajan AK, Ando K, Mukai A, Takahashi M, Suenaga Y, Ohira M, Koda T, Hirota T, Ozaki T, Nakagawara A: KIF1Bbeta functions as a haploinsufficient tumor suppressor gene mapped to chromosome 1p36.2 by inducing apoptotic cell death. J Biol Chem 2008, 283:24426-24434.
28. Attiyeh EF, London WB, Mosse YP, Wang Q, Winter C, Khazi D, McGrady PW, Seeger RC, Look AT, Shimada H, Brodeur GM, Cohn SL, Matthay KK, Maris JM: Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med 2005, 353:2243-2253.
29. Caron H, van Sluis P, de Kraker J, Bokkerink J, Egeler M, Laureys G, Slater R, Westerveld A, Voute PA, Versteeg R: Allelic loss of chromosome 1p as a predictor of unfavora-ble outcome in patients with neuroblastoma. N Engl J Med 1996, 334:225-230.
30. Gehring M, Berthold F, Edler L, Schwab M, Amler LC: The 1p deletion is not a reliable marker for the prognosis of patients with neuroblastoma. Cancer Res 1995, 55:5366-5369.
31. Meddeb M, Danglot G, Chudoba I, Venuat AM, Benard J, Avet-Loiseau H, Vasseur B, Le Paslier D, Terrier-Lacombe MJ, Hartmann O, Bernheim A: Additional copies of a 25 Mb chro-mosomal region originating from 17q23.1-17qter are present in 90% of high-grade neuroblastomas. Genes Chromosomes Cancer 1996, 17:156-165.
32. Van Roy N, Laureys G, Cheng NC, Willem P, Opdenakker G, Versteeg R, Speleman F: 1;17 translocations and other chromosome 17 rearrangements in human primary neu-roblastoma tumors and cell lines. Genes Chromosomes Cancer 1994, 10:103-114.
33. Caron H, van Sluis P, van Roy N, de Kraker J, Speleman F, Voute PA, Westerveld A, Slater R, Versteeg R: Recurrent 1;17 translocations in human neuroblastoma reveal nonhomol-ogous mitotic recombination during the S/G2 phase as a novel mechanism for loss of heterozygosity. Am J Hum Genet 1994, 55:341-347.
34. Savelyeva L, Corvi R, Schwab M: Translocation involving 1p and 17q is a recurrent genetic alteration of human neurob-lastoma cells. Am J Hum Genet 1994, 55:334-340.
35. Laureys G, Speleman F, Opdenakker G, Benoit Y, Leroy J: Constitutional translocation t(1;17)(p36;q12-21) in a patient with neuroblastoma. Genes Chromosomes Cancer 1990, 2: 252-254.
36. Laureys G, Speleman F, Versteeg R, van der Drift P, Chan A, Leroy J, Francke U, Opdenakker G, Van Roy N: Constitutional translocation t(1;17)(p36.31-p36.13;q11.2-q12.1) in a neu-roblastoma patient. Establishment of somatic cell hybrids and identification of PND/A12M2 on chromosome 1 and NF1/SCYA7 on chromosome 17 as breakpoint flanking single copy markers. Oncogene 1995, 10:1087-1093.
37. Vandepoele K, Andries V, Van Roy N, Staes K, Vandesompele J, Laureys G, De Smet E, Berx G, Speleman F, van Roy F: A constitutional translocation t(1;17)(p36.2;q11.2) in a neu-roblastoma patient disrupts the human NBPF1 and ACCN1 genes. PLoS ONE 2008, 3:e2207.
38. Vandesompele J, Michels E, De Preter K, Menten B, Schramm A, Eggert A, Ambros PF, Combaret V, Francotte N, Antonacci F, De Paepe A, Laureys G, Speleman F, Van Roy N: Identification of 2 putative critical segments of 17q gain in neuroblastoma through integrative genomics. Int J Cancer 2008, 122:1177-1182.
39. Bown N, Cotterill S, Lastowska M, O'Neill S, Pearson AD, Plantaz D, Meddeb M, Danglot G, Brinkschmidt C, Christiansen H, Laureys G, Speleman F, Nicholson J, Bernheim A, Betts DR, Vandesompele J, Van Roy N: Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. N Engl J Med 1999, 340:1954-1961.
40. Vandesompele J, Baudis M, De Preter K, Van Roy N, Ambros P, Bown N, Brinkschmidt C, Christiansen H, Combaret V, Lastowska M, Nicholson J, O'Meara A, Plantaz D, Stallings R, Brichard B, Van den Broecke C, De Bie S, De Paepe A, Laureys G, Speleman F: Unequivocal delineation of clinico-genetic subgroups and development of a new model for improved outcome prediction in neuroblastoma. J Clin Oncol 2005, 23:2280-2299.
41. Adida C, Berrebi D, Peuchmaur M, Reyes-Mugica M, Altieri DC: Anti-apoptosis gene, survivin, and prognosis of neu-roblastoma. Lancet 1998, 351:882-883.
42. Godfried MB, Veenstra M, v Sluis P, Boon K, v Asperen R, Hermus MC, v Schaik BD, Voute TP, Schwab M, Versteeg R, Caron HN: The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1 and nm23-H2. Oncogene 2002, 21:2097-2101.
43. Vandesompele J, Speleman F, Van Roy N, Laureys G, Brinskchmidt C, Christiansen H, Lampert F, Lastowska M, Bown N, Pearson A, Nicholson JC, Ross F, Combaret V, Delattre O, Feuerstein BG, Plantaz D: Multicentre analysis of patterns of DNA gains and losses in 204 neuroblastoma tumors: how many genetic subgroups are there? Med Pediatr Oncol 2001, 36:5-10.
44. McArdle L, McDermott M, Purcell R, Grehan D, O'Meara A, Breatnach F, Catchpoole D, Culhane AC, Jeffery I, Gallagher WM, Stallings RL: Oligonucleotide microarray analysis of gene expression in neuroblastoma displaying loss of chro-mosome 11q. Carcinogenesis 2004, 25:1599-1609.
45. Ando K, Ohira M, Ozaki T, Nakagawa A, Akazawa K, Suenaga Y, Nakamura Y, Koda T, Kamijo T, Murakami Y, Nakagawara A: Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome 11q23, is downregulated in unfa-vorable neuroblastoma without promoter hypermethyla-tion. Int J Cancer 2008, 123:2087-2094.
46. Michels E, Hoebeeck J, De Preter K, Schramm A, Brichard B, De Paepe A, Eggert A, Laureys G, Vandesompele J, Speleman F: CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC Cancer 2008, 8:173.
47. Nowacki S, Skowron M, Oberthuer A, Fagin A, Voth H, Brors B, Westermann F, Eggert A, Hero B, Berthold F, Fischer M: Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell sur-vival in neuroblastoma. Oncogene 2008, 27:3329-3338.
48. Breen CJ, O'Meara A, McDermott M, Mullarkey M, Stallings RL: Coordinate deletion of chromosome 3p and 11q in neu-roblastoma detected by comparative genomic hybridiza-tion. Cancer Genet Cytogenet 2000, 120:44-49.
49. Ejeskar K, Aburatani H, Abrahamsson J, Kogner P, Martinsson T: Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT gene. Br J Cancer 1998, 77:1787-1791.
50. Luttikhuis ME, Powell JE, Rees SA, Genus T, Chughtai S, Ramani P, Mann JR, McConville CM: Neuroblastomas with chromosome 11q loss and single copy MYCN comprise a biologically distinct group of tumours with adverse prog-nosis. Br J Cancer 2001, 85:531-537.
51. Plantaz D, Vandesompele J, Van Roy N, Lastowska M, Bown N, Combaret V, Favrot MC, Delattre O, Michon J, Benard J, Hartmann O, Nicholson JC, Ross FM, Brinkschmidt C, Laureys G, Caron H, Matthay KK, Feuerstein BG, Speleman F: Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q dele-tion in tumors lacking MYCN amplification. Int J Cancer 2001, 91:680-686.
52. Hoebeeck J, Michels E, Menten B, Van Roy N, Eggert A, Schramm A, De Preter K, Yigit N, De Smet E, De Paepe A, Laureys G, Vandesompele J, Speleman F: High resolution til-ing-path BAC array deletion mapping suggests commonly involved 3p21-p22 tumor suppressor genes in neuroblast-oma and more frequent tumors. Int J Cancer 2007, 120:533-538.
53. Longo L, Panza E, Schena F, Seri M, Devoto M, Romeo G, Bini C, Pappalardo G, Tonini GP, Perri P: Genetic predisposition to familial neuroblastoma: identification of two novel genomic regions at 2p and 12p. Hum Hered 2007, 63:205-211.
54. Shojaei-Brosseau T, Chompret A, Abel A, de Vathaire F, Raquin MA, Brugieres L, Feunteun J, Hartmann O, Bonaiti-Pellie C: Genetic epidemiology of neuroblastoma: a study of 426 cases at the Institut Gustave-Roussy in France. Pediatr Blood Cancer 2004, 42:99-105.
55. Knudson AG Jr, Strong LC: Mutation and cancer: neuroblas-toma and pheochromocytoma. Am J Hum Genet 1972, 24: 514-532.
56. Amiel J, Laudier B, Attie-Bitach T, Trang H, de Pontual L, Gener B, Trochet D, Etchevers H, Ray P, Simonneau M, Vekemans M, Munnich A, Gaultier C, Lyonnet S: Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syn-drome. Nat Genet 2003, 33:459-461.
57. Mosse YP, Laudenslager M, Khazi D, Carlisle AJ, Winter CL, Rappaport E, Maris JM: Germline PHOX2B mutation in hereditary neuroblastoma. Am J Hum Genet 2004, 75:727-730.
58. Trochet D, Bourdeaut F, Janoueix-Lerosey I, Deville A, de Pontual L, Schleiermacher G, Coze C, Philip N, Frebourg T, Munnich A, Lyonnet S, Delattre O, Amiel J: Germline muta-tions of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Am J Hum Genet 2004, 74:761-764.
59. Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM: Identification of ALK as a major familial neurob-lastoma predisposition gene. Nature 2008, 455:930-935.
60. Caren H, Abel F, Kogner P, Martinsson T: High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochem J 2008, 416:153-159.
61. Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa S: Oncogenic mutations of ALK kinase in neuroblastoma. Nature 2008, 455:971-974.
62. George RE, Sanda T, Hanna M, Frohling S, Luther W 2nd, Zhang J, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregor VE, Webb TR, Gray NS, Gilliland DG, Diller L, Greulich H, Morris SW, Meyerson M, Look AT: Activating mutations in ALK provide a therapeutic target in neurob-lastoma. Nature 2008, 455:975-978.
63. Janoueix-Lerosey I, Lequin D, Brugieres L, Ribeiro A, de Pontual L, Combaret V, Raynal V, Puisieux A, Schleiermacher G, Pierron G, Valteau-Couanet D, Frebourg T, Michon J, Lyonnet S, Amiel J, Delattre O: Somatic and germline activat-ing mutations of the ALK kinase receptor in neuroblast-oma. Nature 2008, 455:967-970.
64. Maris JM, Mosse YP, Bradfield JP, Hou C, Monni S, Scott RH, Asgharzadeh S, Attiyeh EF, Diskin SJ, Laudenslager M, Winter C, Cole KA, Glessner JT, Kim C, Frackelton EC, Casalunovo T, Eckert AW, Capasso M, Rappaport EF, McConville C, London WB, Seeger RC, Rahman N, Devoto M, Grant SF, Li H, Hakonarson H: Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N Engl J Med 2008, 358: 2585-2593.
65. Capasso M, Devoto M, Hou C, Asgharzadeh S, Glessner JT, Attiyeh EF, Mosse YP, Kim C, Diskin SJ, Cole KA, Bosse K, Diamond M, Laudenslager M, Winter C, Bradfield JP, Scott RH, Jagannathan J, Garris M, McConville C, London WB, Seeger RC, Grant SF, Li H, Rahman N, Rappaport E, Hakonarson H, Maris JM: Common variations in BARD1 influence suscep-tibility to high-risk neuroblastoma. Nat Genet 2009, 41:718-723.
66. Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL, Yang MC, Hwang LY, Bowcock AM, Baer R: Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat Genet 1996, 14:430-440.
67. Kallioniemi OP, Kallioniemi A, Piper J, Isola J, Waldman FM, Gray JW, Pinkel D: Optimizing comparative genomic hybrid-ization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer 1994, 10: 231-243.
68. Michels E, Vandesompele J, De Preter K, Hoebeeck J, Vermeulen J, Schramm A, Molenaar JJ, Menten B, Marques B, Stallings RL, Combaret V, Devalck C, De Paepe A, Versteeg R, Eggert A, Laureys G, Van Roy N, Speleman F: ArrayCGH-based classification of neuroblastoma into genomic sub-groups. Genes Chromosomes Cancer 2007, 46:1098-1108.
69. Janoueix-Lerosey I, Schleiermacher G, Michels E, Mosseri V, Ribeiro A, Lequin D, Vermeulen J, Couturier J, Peuchmaur M, Valent A, Plantaz D, Rubie H, Valteau-Couanet D, Thomas C, Combaret V, Rousseau R, Eggert A, Michon J, Speleman F, Delattre O: Overall genomic pattern is a predictor of outcome in neuroblastoma. J Clin Oncol 2009, 27:1026-1033.
70. Mosse YP, Diskin SJ, Wasserman N, Rinaldi K, Attiyeh EF, Cole K, Jagannathan J, Bhambhani K, Winter C, Maris JM: Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression. Genes Chromosomes Cancer 2007, 46:936-949.
71. Vandesompele J, Van Roy N, Van Gele M, Laureys G, Ambros P, Heimann P, Devalck C, Schuuring E, Brock P, Otten J, Gyselinck J, De Paepe A, Speleman F: Genetic heterogeneity of neuroblastoma studied by comparative genomic hybrid-ization. Genes Chromosomes Cancer 1998, 23:141-152.
72. Michels E, De Preter K, Van Roy N, Speleman F: Detection of DNA copy number alterations in cancer by array compara-tive genomic hybridization. Genet Med 2007, 9:574-584.
73. Tomioka N, Oba S, Ohira M, Misra A, Fridlyand J, Ishii S, Nakamura Y, Isogai E, Hirata T, Yoshida Y, Todo S, Kaneko Y, Albertson DG, Pinkel D, Feuerstein BG, Nakagawara A: Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular sig-nature. Oncogene 2008, 27:441-449.
74. Asgharzadeh S, Pique-Regi R, Sposto R, Wang H, Yang Y, Shimada H, Matthay K, Buckley J, Ortega A, Seeger RC: Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplifica-tion. J Natl Cancer Inst 2006, 98:1193-1203.
75. Oberthuer A, Berthold F, Warnat P, Hero B, Kahlert Y, Spitz R, Ernestus K, Konig R, Haas S, Eils R, Schwab M, Brors B, Westermann F, Fischer M: Customized oligonucleotide microarray gene expression-based classification of neu-roblastoma patients outperforms current clinical risk strat-ification. J Clin Oncol 2006, 24:5070-5078.
76. Ohira M, Oba S, Nakamura Y, Isogai E, Kaneko S, Nakagawa A, Hirata T, Kubo H, Goto T, Yamada S, Yoshida Y, Fuchioka M, Ishii S, Nakagawara A: Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of inter-mediate risk neuroblastomas. Cancer Cell 2005, 7:337-350.
77. Schramm A, Schulte JH, Klein-Hitpass L, Havers W, Sieverts H, Berwanger B, Christiansen H, Warnat P, Brors B, Eils J, Eils R, Eggert A: Prediction of clinical outcome and biological characterization of neuroblastoma by expression profiling. Oncogene 2005, 24:7902-7912.
78. Wei JS, Greer BT, Westermann F, Steinberg SM, Son CG, Chen QR, Whiteford CC, Bilke S, Krasnoselsky AL, Cenacchi N, Catchpoole D, Berthold F, Schwab M, Khan J: Prediction of clinical outcome using gene expression profiling and artifi-cial neural networks for patients with neuroblastoma. Cancer Res 2004, 64:6883-6891.
79. Berwanger B, Hartmann O, Bergmann E, Bernard S, Nielsen D, Krause M, Kartal A, Flynn D, Wiedemeyer R, Schwab M, Schafer H, Christiansen H, Eilers M: Loss of a FYN-regulated differentiation and growth arrest pathway in advanced stage neuroblastoma. Cancer Cell 2002, 2:377-386.
80. Vermeulen J, De Preter K, Naranjo A, Vercruysse L, Van Roy N, Hellemans J, Swerts K, Bravo S, Scaruffi P, Tonini GP, De Bernardi B, Noguera R, Piqueras M, Canete A, Castel V, Janoueix-Lerosey I, Delattre O, Schleiermacher G, Michon J, Combaret V, Fischer M, Oberthuer A, Ambros PF, Beiske K, Benard J, Marques B, Rubie H, Kohler J, Potschger U, Ladenstein R, et al.: Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study. Lancet Oncol 2009, 10:663-671.
81. De Preter K, Vandesompele J, Heimann P, Yigit N, Beckman S, Schramm A, Eggert A, Stallings RL, Benoit Y, Renard M, De Paepe A, Laureys G, Pahlman S, Speleman F: Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes. Genome Biol 2006, 7:R84.
82. Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, Reich M, Hieronymus H, Wei G, Armstrong SA, Haggarty SJ, Clemons PA, Wei R, Carr SA, Lander ES, Golub TR: The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 2006, 313:1929-1935.
83. De Preter K, De Brouwer S, Van Maerken T, Pattyn F, Schramm A, Eggert A, Vandesompele J, Speleman F: Meta-mining of neuroblastoma and neuroblast gene expression profiles reveals candidate therapeutic compounds. Clin Cancer Res 2009, 15:3690-3696.
84. Ongenaert M, Van Neste L, De Meyer T, Menschaert G, Bekaert S, Van Criekinge W: PubMeth: a cancer methylation database combining text-mining and expert annotation. Nucleic Acids Res 2008, 36:D842- D846.
85. Abe M, Ohira M, Kaneda A, Yagi Y, Yamamoto S, Kitano Y, Takato T, Nakagawara A, Ushijima T: CpG island methylator phenotype is a strong determinant of poor prognosis in neuroblastomas. Cancer Res 2005, 65:828-834.
86. Alaminos M, Davalos V, Cheung NK, Gerald WL, Esteller M: Clustering of gene hypermethylation associated with clini-cal risk groups in neuroblastoma. J Natl Cancer Inst 2004, 96: 1208-1219.
87. Banelli B, Gelvi I, Di Vinci A, Scaruffi P, Casciano I, Allemanni G, Bonassi S, Tonini GP, Romani M: Distinct CpG methyla-tion profiles characterize different clinical groups of neu-roblastic tumors. Oncogene 2005, 24:5619-5628.
88. Hoebeeck J, Michels E, Pattyn F, Combaret V, Vermeulen J, Yigit N, Hoyoux C, Laureys G, De Paepe A, Speleman F, Vandesompele J: Aberrant methylation of candidate tumor suppressor genes in neuroblastoma. Cancer Lett 2009, 273: 336-346.
89. Yang Q, Kiernan CM, Tian Y, Salwen HR, Chlenski A, Brumback BA, London WB, Cohn SL: Methylation of CASP8, DCR2, and HIN-1 in neuroblastoma is associated with poor outcome. Clin Cancer Res 2007, 13:3191-3197.
90. Misawa A, Tanaka S, Yagyu S, Tsuchiya K, Iehara T, Sugimoto T, Hosoi H: RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker. Br J Cancer 2009, 100:399-404.
91. Yagyu S, Gotoh T, Iehara T, Miyachi M, Katsumi Y, Tsubai-Shimizu S, Kikuchi K, Tamura S, Tsuchiya K, Imamura T, Misawa-Furihata A, Sugimoto T, Sawada T, Hosoi H: Circulating methylated-DCR2 gene in serum as an indica-tor of prognosis and therapeutic efficacy in patients with MYCN nonamplified neuroblastoma. Clin Cancer Res 2008, 14: 7011-7019.
92. Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006, 6:259-269.
93. Chen Y, Stallings RL: Differential patterns of microRNA expression in neuroblastoma are correlated with progno-sis, differentiation, and apoptosis. Cancer Res 2007, 67: 976-983.
94. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR: MicroRNA expression profiles classify human cancers. Nature 2005, 435:834-838.
95. Schulte JH, Horn S, Otto T, Samans B, Heukamp LC, Eilers UC, Krause M, Astrahantseff K, Klein-Hitpass L, Buettner R, Schramm A, Christiansen H, Eilers M, Eggert A, Berwanger B: MYCN regulates oncogenic microRNAs in neuroblastoma. Int J Cancer 2008, 122:699-704.
96. Otto T, Horn S, Brockmann M, Eilers U, Schuttrumpf L, Popov N, Kenney AM, Schulte JH, Beijersbergen R, Christiansen H, Berwanger B, Eilers M: Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell 2009, 15:67-78.
97. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T: A polycistronic microRNA cluster, miR-17-92, is overex-pressed in human lung cancers and enhances cell prolifer-ation. Cancer Res 2005, 65:9628-9632.
98. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT: c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005, 435:839-843.
99. Uziel T, Karginov FV, Xie S, Parker JS, Wang YD, Gajjar A, He L, Ellison D, Gilbertson RJ, Hannon G, Roussel MF: The miR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci USA 2009, 106: 2812-2817.
100. Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, Boldrini R, Donfrancesco A, Federici V, Giacomini P, Peschle C, Fruci D: Antagomir-17-5p abolishes the growth of ther-apy-resistant neuroblastoma through p21 and BIM. PLoS ONE 2008, 3:e2236.
101. Wei JS, Song YK, Durinck S, Chen QR, Cheuk AT, Tsang P, Zhang Q, Thiele CJ, Slack A, Shohet J, Khan J: The MYCN oncogene is a direct target of miR-34a. Oncogene 2008, 27: 5204-5213.
102. Bilke S, Chen QR, Wei JS, Khan J: Whole chromosome alter-ations predict survival in high-risk neuroblastoma without MYCN amplification. Clin Cancer Res 2008, 14:5540-5547.
103. Welch C, Chen Y, Stallings RL: MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neu-roblastoma cells. Oncogene 2007, 26:5017-5022.
104. Maris JM, Hogarty MD, Bagatell R, Cohn SL: Neuroblastoma. Lancet 2007, 369:2106-2120.
105. Wagner LM, Danks MK: New therapeutic targets for the treatment of high-risk neuroblastoma. J Cell Biochem 2009, 107: 46-57.
106. Darnell JE Jr: Transcription factors as targets for cancer therapy. Nat Rev Cancer 2002, 2:740-749.
107. Lu X, Pearson A, Lunec J: The MYCN oncoprotein as a drug development target. Cancer Lett 2003, 197:125-130.
108. Mo H, Henriksson M: Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation. Proc Natl Acad Sci USA 2006, 103:6344-6349.
109. Mo H, Vita M, Crespin M, Henriksson M: Myc overexpression enhances apoptosis induced by small molecules. Cell Cycle 2006, 5:2191-2194.
110. Burkhart CA, Cheng AJ, Madafiglio J, Kavallaris M, Mili M, Marshall GM, Weiss WA, Khachigian LM, Norris MD, Haber M: Effects of MYCN antisense oligonucleotide administration on tumorigenesis in a murine model of neuroblastoma. J Natl Cancer Inst 2003, 95:1394-1403.
111. Negroni A, Scarpa S, Romeo A, Ferrari S, Modesti A, Raschella G: Decrease of proliferation rate and induction of differen-tiation by a MYCN antisense DNA oligomer in a human neuroblastoma cell line. Cell Growth Differ 1991, 2:511-518.
112. Kang JH, Rychahou PG, Ishola TA, Qiao J, Evers BM, Chung DH: MYCN silencing induces differentiation and apoptosis in human neuroblastoma cells. Biochem Biophys Res Commun 2006, 351:192-197.
113. Nara K, Kusafuka T, Yoneda A, Oue T, Sangkhathat S, Fukuzawa M: Silencing of MYCN by RNA interference induces growth inhibition, apoptotic activity and cell differ-entiation in a neuroblastoma cell line with MYCN amplifica-tion. Int J Oncol 2007, 30:1189-1196.
114. Caren H, Erichsen J, Olsson L, Enerback C, Sjoberg RM, Abrahamsson J, Kogner P, Martinsson T: High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblast-oma tumors: four cases of homozygous deletions of the CDKN2A gene. BMC Genomics 2008, 9:353.
115. Carr J, Bell E, Pearson AD, Kees UR, Beris H, Lunec J, Tweddle DA: Increased frequency of aberrations in the p53/ MDM2/p14(ARF) pathway in neuroblastoma cell lines established at relapse. Cancer Res 2006, 66:2138-2145.
116. Cattelani S, Defferrari R, Marsilio S, Bussolari R, Candini O, Corradini F, Ferrari-Amorotti G, Guerzoni C, Pecorari L, Menin C, Bertorelle R, Altavista P, McDowell HP, Boldrini R, Dominici C, Tonini GP, Raschella G, Calabretta B: Impact of a single nucleotide polymorphism in the MDM2 gene on neuroblas-toma development and aggressiveness: results of a pilot study on 239 patients. Clin Cancer Res 2008, 14:3248-3253.
117. Cui H, Hu B, Li T, Ma J, Alam G, Gunning WT, Ding HF: Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. Am J Pathol 2007, 170:1370-1378.
118. Perfumo C, Parodi S, Mazzocco K, Defferrari R, Inga A, Haupt R, Fronza G, Tonini GP: Impact of MDM2 SNP309 genotype on progression and survival of stage 4 neuroblastoma. Eur J Cancer 2008, 44:2634-2639.
119. Slack A, Chen Z, Tonelli R, Pule M, Hunt L, Pession A, Shohet JM: The p53 regulatory gene MDM2 is a direct transcrip-tional target of MYCN in neuroblastoma. Proc Natl Acad Sci USA 2005, 102:731-736.
120. Thompson PM, Maris JM, Hogarty MD, Seeger RC, Reynolds CP, Brodeur GM, White PS: Homozygous deletion of CDKN2A (p16INK4a/p14ARF) but not within 1p36 or at other tumor suppressor loci in neuroblastoma. Cancer Res 2001, 61:679-686.
121. Valsesia-Wittmann S, Magdeleine M, Dupasquier S, Garin E, Jallas AC, Combaret V, Krause A, Leissner P, Puisieux A: Oncogenic cooperation between H-Twist and N-Myc over-rides failsafe programs in cancer cells. Cancer Cell 2004, 6:625-630.
122. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA: In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004, 303:844-848.
123. Van Maerken T, Speleman F, Vermeulen J, Lambertz I, De Clercq S, De Smet E, Yigit N, Coppens V, Philippe J, De Paepe A, Marine JC, Vandesompele J: Small-molecule MDM2 antagonists as a new therapy concept for neuroblastoma. Cancer Res 2006, 66:9646-9655.
124. Barbieri E, Mehta P, Chen Z, Zhang L, Slack A, Berg S, Shohet JM: MDM2 inhibition sensitizes neuroblastoma to chemo-therapy-induced apoptotic cell death. Mol Cancer Ther 2006, 5:2358-2365.
125. Michaelis M, Rothweiler F, Klassert D, von Deimling A, Weber K, Fehse B, Kammerer B, Doerr HW, Cinatl J Jr: Reversal of P-glycoprotein-mediated multidrug resistance by the murine double minute 2 antagonist nutlin-3. Cancer Res 2009, 69:416-421.
126. Osajima-Hakomori Y, Miyake I, Ohira M, Nakagawara A, Nakagawa A, Sakai R: Biological role of anaplastic lym-phoma kinase in neuroblastoma. Am J Pathol 2005, 167: 1-7-X 213-222.
127. Zhang J, Yang PL, Gray NS: Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2009, 9:28-39.
128. McDermott U, Iafrate AJ, Gray NS, Shioda T, Classon M, Maheswaran S, Zhou W, Choi HG, Smith SL, Dowell L, Ulkus LE, Kuhlmann G, Greninger P, Christensen JG, Haber DA, Settleman J: Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. Cancer Res 2008, 68:3389-3395.
129. Li R, Morris SW: Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. Med Res Rev 2008, 28:372-412.